Methods of modulating immune function

Abstract

Presented herein are therapeutic agents that modulate one or more immune functions and uses of such therapeutic agents in the prevention, treatment and management of diseases. In one aspect, the therapeutic agents modulate one or more signal transduction pathways induced by the binding of B7-H7 to B7-HrCR, or the binding of B7-H2 to either ICOS, CD28, or CTLA-4. In another aspect, the therapeutic agents modulate the binding of B7-H7 to B7-H7CR, or the binding of B7-H2 to either ICOS, CD28, or CTLA-4. The therapeutic agents can be used in the prevention, treatment and/or management of diseases in which it might be useful to modulate one or more immune functions (e.g., cancer, infectious disease, autoimmune disease, and transplantation rejection). In another aspect, presented herein are methods for identifying receptor-ligand interactions.

I claim: 
     
       1. A method enhancing CD4+ T lymphocyte proliferation in a subject with cancer comprising administering to a subject with cancer a pharmaceutical composition comprising an antibody, or fragment thereof, that specifically binds to a human B7-H7CR comprising an amino acid sequence of SEQ ID NO: 5 or SEQ ID NO: 20, and a pharmaceutically acceptable carrier in an amount effective to treat the cancer. 
     
     
       2. The method of  claim 1 , wherein the antibody, or fragment thereof, agonizes a function of human B7-H7CR upon specifically binding to the human B7-H7CR, wherein the function of the human B7-H7CR is:
 (i) binding to human B7-H7 (SEQ ID NO: 3); 
 (ii) enhancement of a signal transduction pathway inducing activity of human B7-H7CR; 
 (iii) enhancement of T lymphocyte proliferation; or 
 (iv) enhancement of immune function. 
 
     
     
       3. The method of  claim 2 , wherein the method enhances immune function. 
     
     
       4. The method of  claim 3 , wherein the immune function is an immune response against cancer cells. 
     
     
       5. The method of  claim 2 , wherein the method enhances a signal transduction pathway inducing activity of human B7-H7CR. 
     
     
       6. The method of  claim 2 , wherein the cancer is selected from the group consisting of leukemia, lymphoma, melanoma, colon cancer, lung cancer, breast cancer, prostate cancer, cervical cancer, liver cancer, testicular cancer, brain cancer, pancreatic cancer, and renal cancer. 
     
     
       7. The method of  claim 1 , wherein the pharmaceutical composition is administered by an oral, intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, sublingual, intranasal, intracerebral, intravaginal, transdermal, rectal, pulmonary, intratumoral, topical, intraventricular, intrathecal, or epidural mode of administration. 
     
     
       8. The method of  claim 1 , wherein the method further comprises one or more additional therapies. 
     
     
       9. The method of  claim 8 , wherein the one or more additional therapies is selected from the group consisting of administering to the subject one or more anti-cancer agents, cytokines, cellular vaccines, or anti- hormonal agents; surgery; chemotherapy; and radiation therapy. 
     
     
       10. The method of  claim 1 , wherein the pharmaceutical composition comprises one or more anti-cancer agents, cytokines, cellular vaccines, or anti-hormonal agents. 
     
     
       11. The method of  claim 1 , wherein the antibody is a monoclonal or polyclonal antibody, or antigen binding fragment thereof. 
     
     
       12. The method of  claim 1 , wherein the antibody is a bispecific or multispecific antibody, or antigen binding fragment thereof. 
     
     
       13. The method of  claim 1 , wherein the antibody is a humanized, human, mouse, or chimeric antibody, or antigen binding fragment thereof. 
     
     
       14. The method of  claim 1 , wherein the antibody is an antigen binding fragment selected from the group consisting of single domain antibodies, single-chain Fvs (scFv), single chain antibodies, Fab fragments, F(ab′) fragments, and disulfide-linked bispecific Fvs (sdFv). 
     
     
       15. A method for increasing an immune response in a subject with cancer comprising administering to the subject with cancer a pharmaceutical composition comprising an antibody, or fragment thereof, that specifically binds to a human B7-H7CR comprising an amino acid sequence of SEQ ID NO: 5 or SEQ ID NO: 20 in an amount effective to increase an immune response. 
     
     
       16. The method of  claim 15 , wherein the immune response is against cancer cells. 
     
     
       17. A method for increasing T lymphocyte proliferation in a subject with cancer comprising administering to a subject with cancer a pharmaceutical composition comprising an antibody, or fragment thereof, that specifically binds to a human B7-H7CR comprising an amino acid sequence of SEQ ID NO: 5 or SEQ ID NO: 20 in an amount effective to increase T lymphocyte proliferation in the subject. 
     
     
       18. The method of  claim 17 , wherein the T lymphocyte proliferation is effective to induce or increase an immune response against cancer cells.